Zhang Zhengwei, Ye Juan, Liu Xinyu, Zhao Wenjing, Zhao Bing, Gao Xuejiao, Lan Hongli, Wu Yuze, Yang Yang, Cao Peng
Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100#, Hongshan Road, Nanjing, 210028, China.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Chin Med. 2023 Sep 7;18(1):114. doi: 10.1186/s13020-023-00826-5.
Oxaliplatin-induced peripheral neurotoxicity (OIPN) limits the dose of chemotherapy and seriously affects the quality of life. Huangqi Guizhi Wuwu Decoction (HGWD) is a classical Traditional Chinese Medicine (TCM) formula for the prevention of OIPN. However, its specific pharmacological mechanism of action remains unknown. Our study found that HGWD can effectively alleviate chronic OIPN and regulate intestinal flora. Therefore, we explored the mechanism of action of HGWD in alleviating chronic OIPN from the perspective of intestinal flora.
In this study, we established an OIPN model in C57BL/6 mice treated with different concentrations of HGWD. Mechanical pain and cold pain were assessed at certain time points, and samples of mice colon, dorsal root ganglion (DRG), serum, and feces were collected. Associated inflammation levels in the colon and DRG were detected using immunohistochemical techniques; the serum lipopolysaccharide (LPS) levels and associated inflammation were assessed using the appropriate kits; and 16S rRNA sequencing was used to examine the dynamic changes in gut microorganisms. Finally, established fecal microbiota transplantation (FMT) and antibiotic (ABX) pretreatment models were used to validate flora's role in HGWD for chronic OIPN by pain scoring and related pathological analysis.
HGWD treatment significantly alleviated pain sensitivity in chronic OIPN mice. Pathological results showed that HGWD treatment improved intestinal ZO-1 expression and reduced serum LPS levels and associated inflammatory factors in the colon, serum, and DRG. The 16S rRNA results showed that HGWD restored the composition of the intestinal flora in a time-dependent manner to alleviate OIPN. FMT and ABX experiments demonstrated that HGWD can alleviate chronic OIPN by regulating intestinal flora homeostasis.
HGWD prevents chronic OIPN by dynamically regulating intestinal flora homeostasis, thereby ameliorating intestinal barrier damage and reducing serum LPS and relevant inflammatory factor levels in the colon, serum, and DRG.
奥沙利铂诱导的周围神经毒性（OIPN）限制了化疗剂量，并严重影响生活质量。黄芪桂枝五物汤（HGWD）是预防OIPN的经典中药方剂。然而，其具体的药理作用机制尚不清楚。我们的研究发现HGWD可有效减轻慢性OIPN并调节肠道菌群。因此，我们从肠道菌群的角度探讨了HGWD减轻慢性OIPN的作用机制。
在本研究中，我们在接受不同浓度HGWD治疗的C57BL/6小鼠中建立了OIPN模型。在特定时间点评估机械性疼痛和冷痛，并收集小鼠结肠、背根神经节（DRG）、血清和粪便样本。使用免疫组化技术检测结肠和DRG中的相关炎症水平；使用适当的试剂盒评估血清脂多糖（LPS）水平和相关炎症；并使用16S rRNA测序检查肠道微生物的动态变化。最后，通过疼痛评分和相关病理分析，利用建立的粪便微生物群移植（FMT）和抗生素（ABX）预处理模型来验证菌群在HGWD治疗慢性OIPN中的作用。
HGWD治疗显著减轻了慢性OIPN小鼠的疼痛敏感性。病理结果显示，HGWD治疗改善了肠道紧密连接蛋白1（ZO-1）的表达，降低了结肠、血清和DRG中的血清LPS水平及相关炎症因子。16S rRNA结果显示，HGWD以时间依赖性方式恢复肠道菌群组成以减轻OIPN。FMT和ABX实验表明，HGWD可通过调节肠道菌群稳态来减轻慢性OIPN。
HGWD通过动态调节肠道菌群稳态来预防慢性OIPN，从而改善肠道屏障损伤，降低结肠、血清和DRG中的血清LPS及相关炎症因子水平。
